A Phase I/II Trial of a Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naïve Children

NCT ID: NCT00384670

Last Updated: 2014-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-08-31
• Study Completion Date: 2004-05-31

Brief Summary

To assess the safety, reactogenicity and immunogenicity of two doses of the dengue vaccine in Flavi-virus antibody-naive children between 6 and 9 years of age.

Detailed Description

This study was a Phase I/II, open-label trial with one treatment group; 7, healthy, flavivirus naïve children between the ages of 6 and 7 years residing in Bangkok, Thailand. Seronegative status was determined by measuring neutralizing (N) antibody titers to dengue 1-4 and JE virus (JE) using hemagglutination inhibition (HAI) (1st) and PRNT (2nd) assays. Titers <10 and <10, respectively, were considered negative. Enrolled children received two doses of tetravalent dengue vaccine at study months 0 and 6, and two doses of JE vaccine (study benefit) at study months 7 and 7.5. Enrolled children attended 20 study visits, received 4 injections, and 7 venipunctures (one additional blood sample for screening). In the acute period (1 month) following vaccination, safety was assessed using symptom diary cards and clinical and laboratory evaluations. Viremia was measured 10 days post dengue vaccination. Solicited and unsolicited adverse events were assessed for 30 days following each dengue vaccination. Serious adverse events were assessed throughout the study period. In the case of illness, investigators would complete additional clinical and virologic evaluations. Dengue vaccine immunogenicity was assessed 30 days following each dengue vaccination using the PRNT50 assay. The According to Protocol (ATP) cohort was determined by evaluating the occurrence of intermittent natural dengue infection using ELISA IgM/IgG titer ratios. A long-term follow-up of dengue vaccine recipients is described in a separate protocol (Dengue-005 protocol).

Conditions

Dengue Fever

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Dengue and Japanese Encephalitis vaccine

1 mL subcutaneous injection Dengue Vaccine Formulation 17 on Day 0 and Day 60. 0.5 mL subcutaneous injection Licensed Japanese Encephalitis (JE) Vaccine on months 7 and 7.5.

Group Type: EXPERIMENTAL

Dengue Vaccine Formulation 17

Intervention Type: BIOLOGICAL

Tetravalent live attenuated DEN vaccine candidate. Containing dengue serotypes 1,2, and 3 vaccines produced at the Salk Institute and dengue serotype 4 produced at the WRAIR Pilot Bioproduction Facility. Dosage 1 mL administered via injection at Day 0 and Day 60.

Licensed Japanese Encephalitis (JE) Vaccine

Intervention Type: BIOLOGICAL

Produced by the Thailand GPO using a Beijing strain of JE in liquid form; dosed at 0.5 mL ot 7 and 7.5 months.

Interventions

Dengue Vaccine Formulation 17

Tetravalent live attenuated DEN vaccine candidate. Containing dengue serotypes 1,2, and 3 vaccines produced at the Salk Institute and dengue serotype 4 produced at the WRAIR Pilot Bioproduction Facility. Dosage 1 mL administered via injection at Day 0 and Day 60.

Intervention Type: BIOLOGICAL

Licensed Japanese Encephalitis (JE) Vaccine

Produced by the Thailand GPO using a Beijing strain of JE in liquid form; dosed at 0.5 mL ot 7 and 7.5 months.

Intervention Type: BIOLOGICAL

Other Intervention Names

F17; JE

Eligibility Criteria

Inclusion Criteria

• A male or female child six to nine years of age (greater than or equal to 6 years of age and less than 10 years of age) at the time of the first vaccination.
• Free of obvious health problems as established by medical history and physical examination before entering into the study.
• Seronegative by HAI and screening PRNT for antibodies to dengue types 1-4 and Japanese Encephalitis (JE) virus
• Written informed consents by the parent of the subject for screening and enrollment into the study.

Exclusion Criteria

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose or planned administration during the study (For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
• Use of any investigational or non-registered drug or vaccine other than the protocol-specified vaccines within 30 days preceding the administration of the first dengue vaccine dose or planned use during the study period.
• Planned administration of a vaccine not foreseen by the study protocol and within 30 days prior or after any dengue/JE vaccine administration.
• Any current medical condition determined to be serious by the investigator (e.g. seizures)
• History of chronic headaches or a first order family member (parent or sibling) with a history of chronic headaches
• Abnormal clinical laboratory screening test result (based on normal values set by the laboratory) that is deemed clinically significant by the investigator or Medical Monitor (including seropositivity for HBsAg or anti-HCV)
• Previous vaccination against yellow fever virus, JEV, or tick-borne encephalitis virus (TBE) or existence of any flavivirus antibody
• Any suspected or confirmed immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
• Family history of a congenital or hereditary immunodeficiency
• Acute illness at time of enrollment (defined as the presence of a moderate or severe illness with or without fever). All vaccines can be administered to persons with a minor illness such as diarrhea or mild upper respiratory infection without fever, i.e., oral temperature <37.5°C.
• Administration of immunoglobulins and/or blood products within 6 months prior to study entry or planned administration during the study period
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines (including neomycin, streptomycin, gentamicin, amikacin, tobramycin, kanamycin and bacitracin; allergy to dogs or monkeys or hypersensitivity to proteins of rodent or neural origin or to thimerosal, allergy to porcine gelatin)
• Child whose parent has no easy access to a fixed or mobile telephone
• Plans to move from Bangkok during the first 8.5 months after initial vaccination
• Parental illiteracy.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

U.S. Army Medical Research and Development Command

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MAJ Stephen J Thomas, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Virology USAMC-AFRIMS

Sriluck Simasathien, MD

Role: PRINCIPAL_INVESTIGATOR

Phramongkutklao College of Medicine and Hospital

Locations

Department of Pediatrics, Pharamongkutklao Hospital

Bangkok, , Thailand

Countries

Thailand

References

Simasathien S, Thomas SJ, Watanaveeradej V, Nisalak A, Barberousse C, Innis BL, Sun W, Putnak JR, Eckels KH, Hutagalung Y, Gibbons RV, Zhang C, De La Barrera R, Jarman RG, Chawachalasai W, Mammen MP Jr. Safety and immunogenicity of a tetravalent live-attenuated dengue vaccine in flavivirus naive children. Am J Trop Med Hyg. 2008 Mar;78(3):426-33.

Reference Type: DERIVED

PMID: 18337339 (View on PubMed)

Other Identifiers

HSRRB#A-12189

Identifier Type: OTHER

Identifier Source: secondary_id

GSK Dengue-003

Identifier Type: OTHER

Identifier Source: secondary_id

WRAIR 1048

Identifier Type: -

Identifier Source: org_study_id